STABILITY-MODULATING LINKERS FOR USE WITH ANTIBODY DRUG CONJUGATES

The present invention provides stability-modulated antibody-drug conjugates, stability-modulating linker components used to make these stability-modulated antibody-drug conjugates, and methods of making stability modulating linkers and stability-modulated antibody-drug conjugates.

ANTIBODIES SPECIFIC FOR TROP-2 AND THEIR USES

The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer.

METHODS FOR TREATING BONE CANCER PAIN BY ADMINISTERING A NERVE GROWTH FACTOR ANTAGONIST

The invention features methods and compositions for preventing or treating bone cancer pain including cancer pain associated with bone metastasis by administering an antagonist of nerve growth factor (NGF). The NGF antagonist may be an anti-NGF (such as anti-hNGF) antibody that is capable of binding hNGF.

ENGINEERED POLYPEPTIDE CONJUGATES

The present invention provides engineered polypeptide conjugates (e.g., antibody-drug- conjugates) comprising specific acyl donor glutamine-containing tags and amine donor agents. The invention also provides methods of making such engineered polypeptide conjugates using transglutaminase and methods of using thereof.

ANTIBODY-DRUG CONJUGATES WITH HIGH DRUG LOADING

The present invention provides transglutaminase-mediated antibody-drug conjugates with high antibody-drug ratio (DAR) comprising 1) glutamine-containing tags, endogenous glutamines, and/or endogenous glutamines made reactive by antibody engineering or an engineered transglutaminase (e.g., with altered substrate specifity); and 2) amine donor agents comprising amine donor units, linkers, and agent moieties, wherein the DAR is at least about 5. The invention also provides methods of making and methods of using such higher drug loaded antibody-drug conjugates.

ANTI-NGF ANTIBODIES AND METHODS USING SAME

... ²²²The invention concerns anti-NGF antibodies (such as anti-NGF antagonist ²antibodies), and polynucleotides encoding the same. The invention further ²concerns use of such antibodies and/or polynucleotides in the treatment and/or ²prevention of pain, including post-surgical pain, rheumatoid arthritis pain, ²and osteoarthritis pain.² ...

ANTAGONIST ANTIBODIES DIRECTED AGAINST CALCITONIN GENE-RELATED PEPTIDE AND METHODS USING SAME

The invention features methods for preventing or treating CGRP associated disorders such as vasomotor symptoms, including headaches (e.g., migraine, cluster headache, and tension headache) and hot flushes, by administering an anti-CGRP antagonist antibody. Antagonist antibody G1 and antibodies derived from G1 directed to CGRP are also described.

ANTI-NGF ANTIBODIES AND METHODS USING SAME

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

METHODS OF TREATING OPHTHALMIC DISEASES

Methods of using inhibitors (including monoclonal antibodies) directed against amyloid-beta peptide for the treatment of ophthalmic diseases such as age-related macular degeneration are described.

PCSK9 ANTAGONISTS

The present invention provides antagonizing antibodies, antigen-binding portions thereof, and aptamers that bind to proprotein convertase subtilisin kexin type 9 (PCSK9). Also provided are antibodies directed to peptides, in which the antibodies bind to PCSK9. The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acid. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof to reduce LDL-cholesterol levels and/or for the treatment and/or prevention of cardiovascular disease, including treatment of hypercholesterolemia.

ANTIBODIES SPECIFIC FOR DKK-1 AND THEIR USES

The present invention provides antibodies and fragments thereof that bind to Dkk-1 and, in particular, to humanized antibodies and fragments thereof that bind to Dkk-1 and, even more particularly to fully humanized antibodies and immunologically functional fragments that bind to Dkk-1. Also provided are antibodies and fragments thereof which compete with the binding of an anti-mouse Dkk-1 monoclonal antibody for binding to Dkk-1+ cells. Also provided are nucleic acids encoding anti-Dkk-1 antibodies or fragments thereof, as well as expression vectors and host cells incorporating these nucleic acids for the recombinant expression of anti-Dkk-1 antibodies and fragments thereof. Also provided are methods of preparing the antibodies and fragments thereof of the invention. Also provided are bone anabolic agents. Pharmaceutical compositions comprising the antibodies or fragments thereof of the invention are also provided. Further provided are methods of treating diseases, conditions and disorders ...

STAPHYLOCOCCUS AUREUS SPECIFIC ANTIBODIES AND USES THEREOF

The present invention provides antagonizing antibodies that bind to S. aureus alpha-toxin. The invention further provides a method of obtaining such antibodies and antibody encoding nucleic acids. The invention further relates to therapeutic methods for use of these antibodies for the treatment and/or prevention of staphylococcal disease, including, for example, pneumonia, bacteremia, sepsis, eye infection, and abscess.

Antibodies directed against amyloid-beta peptide and methods using same

Methods of using antibodies directed to the C-terminal side of -amyloid peptide for diagnosing and treatment of Alzheimer's disease and A peptide associated diseases are described.

ANTI-PD-1 ANTIBODIES AND METHODS OF USE THEREOF

The present invention provides antagonizing antibodies that bind to programmed cell death protein 1 (PD-1) and methods of using same. The anti-PD-1 antibodies can be used therapeutically alone or in combination with other therapeutics to treat cancer and other diseases. 138-. (canceled)39. A method for treating cancer in a subject in need thereof , the method comprising administering to the subject (1) an effective amount of an isolated antagonist antibody that specifically binds to PD-1 and comprises:a heavy chain variable region (VH) comprising a VH complementarity determining region one (CDR1), VH CDR2, and VH CDR3 of the VH having an amino acid sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4; SEQ ID NO: 5; and SEQ ID NO: 6; anda light chain variable region (VL) comprising a VL CDR1, VL CDR2, and VL CDR3 of the VL having an amino acid sequence selected from the group consisting of SEQ ID NO: 2; SEQ ID NO:7; SEQ ID NO: 8; and SEQ ID NO: 9,and (2) an effective amount of a vaccine capable of eliciting an immune response against cells of the cancer.40. A method for enhancing the immunogenicity or therapeutic effect of a vaccine administered to a subject for the treatment of cancer , the method comprising administering to the subject receiving the vaccine an effective amount of an isolated antagonist antibody that specifically binds to PD-1 and comprises:a heavy chain variable region (VH) comprising a VH complementarity determining region one (CDR1), VH CDR2, and VH CDR3 of the VH having an amino acid sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4; SEQ ID NO: 5; and SEQ ID NO: 6; anda light chain variable region (VL) comprising a VL CDR1, VL CDR2, and VL CDR3 of the VL having an amino acid sequence selected from the group consisting of SEQ ID NO: 2; SEQ ID NO:7; SEQ ID NO: 8; and SEQ ID NO: 9.41. The method of claim 39 , wherein the cancer is selected from the group consisting of breast cancer claim 39 , gastric ...

VERFAHREN ZUR BEHANDLUNG VON DURCH TAXOL INDUZIERTER SENSORISCHER NEUROPATHIE

USE OF ANTI-NGF ANTIBODY FOR IMPROVING STIFFNESS IN OSTEOARTHRITIS

... ²The invention concerns anti-NGF antibodies (such as anti-NGF antagonist ²antibodies ²e.g. E3 anti-NGF antibody comprising the heavy chain CDRs of SEQ ID NOs: 3-5 ²and the light chain CDRs of SEQ ID NOs: 6-8), and polynucleotides encoding the ²²same. The invention further concerns use of such antibodies and/or ²polynucleotides ²in the treatment and/or prevention of pain, including post-surgical pain, ²rheumatoid ²arthritis pain, and osteoarthritis pain.²² ...

ANTAGONIST IL-7 RECEPTOR ANTIBODIES TO TREAT TYPE 2 DIABETES AND IMMUNOLOGICAL DISORDERS

The present invention provides antagonizing antibodies that bind to interleukin-7 receptor (IL-7R). The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acids. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof for the treatment and/or prevention of type 2 diabetes and immunological disorders, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, graft-versus-host disease, and lupus.

VERFAHREN ZUR SCHMERZBEHANDLUNG IN KNOCHENKREBS DU

ENGINEERED POLYPEPTIDE CONJUGATES

The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates) comprising specific acyl donor glutamine-containing tags and amine donor agents. The invention also provides methods of making such engineered polypeptide conjugates using transglutaminase and methods of using thereof.

ANTI-NGF ANTIBODIES AND METHODS USING SAME

ANTIBODIES DIRECTED AGAINST AMYLOID-BETA PEPTIDE AND METHODS USING SAME

... ²²²Monoclonal antibody 9TL and antibodies derived from 9TL directed against ²amyloid-beta peptide and methods of using same for diagnosing and treatment of ²Alzheimer's disease and A.beta. peptide associated diseases are described. ²Methods of using antibodies directed against amyloid-beta peptide having ²impaired effector function for treatment of Alzheimer's disease and A.beta. ²peptide associated diseases are also described.² ...

Antibodies directed against amyloid-beta peptide a

Anti-NGF antibodies and methods using same

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Anti-PD-1 antibodies and methods of use thereof

The present invention provides antagonizing antibodies that bind to programmed cell death protein 1 (PD-1) and methods of using same. The anti-PD-1 antibodies can be used therapeutically alone or in combination with other therapeutics to treat cancer and other diseases.

HETERODIMERIC PROTEINS AND METHODS FOR PRODUCING AND PURIFYING THEM

The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and other heterodimeric proteins comprising immunoglubulin-like hinge sequences. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided.

ANTIBODIES DIRECTED AGAINST AMYLOID-BETA PEPTIDE AND METHODS USING SAME

Antibodies directed to the C-terminal side of .beta.-amyloid peptide and methods of using these antibodies for diagnosing and treatment of Alzheimer's disease and A.beta. peptide associated diseases are described.

ANTI-NGF ANTIBODIES AND METHODS USING SAME

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Antagonist anti-il-7 receptor antibodies and methods

ANTIBODIES DIRECTED AGAINST AMYLOID-BETA PEPTIDE AND METHODS USING SAME

Methods of using antibodies directed to the C-terminal side of β-amyloid peptide for diagnosing and treatment of Alzheimer's disease and Aβ peptide associated diseases are described.

VERFAHREN ZUR SCHMERZBEHANDLUNG DURCH VERABREICHUNG EINES ANTAGONISTISCHEN ANTIKÖRPERS GEGEN DEN NERVENWACHSTUMFAKTOR UND EINES OPIOID-ANALGETIKUMS SOWIE DIESE ENTHALTENDE ZUSAMMENSETZUNGEN

ANTIBODIES DIRECTED AGAINST AMYLOID-BETA PEPTIDE AND METHODS USING SAME

Antibodies directed to the C-terminal side of β-amyloid peptide and methods of using these antibodies for diagnosing and treatment of Alzheimer's disease and Aβ peptide associated diseases are described. 1. A monoclonal antibody that specifically binds to a β-amyloid peptide or an aggregated form of a β-amyloid peptide , wherein the said antibody binds to an epitope on Aβthat includes amino acids 25-34 and 40 , wherein said antibody binds to Aβwith higher affinity than its binding to Aβand Aβ , wherein said antibody binds to Aβwith a Kof less than 1 μm.2. The antibody of claim 1 , wherein the isotype of the antibody is selected from the group consisting of IgG1 claim 1 , IgG2 claim 1 , IgG3 claim 1 , and IgG4.3. The antibody of claim 1 , wherein N-glycosylation in the Fc region of the antibody is removed.4. The antibody of claim 1 , wherein the heavy chain constant region of the antibody is a human IgG2a constant region comprising amino acid mutations A330P331 to S330S331 claim 1 , wherein the amino acid position is based on Kabat numbering with reference to human wildtype IgG2a sequence.5. A pharmaceutical composition comprising the antibody of and a pharmaceutically acceptable carrier.6. A method for treating a disease associated with aberrant deposition of β-amyloid in a subject claim 1 , comprising administering to the subject an effective amount of an antibody that specifically binds to a β-amyloid peptide or an aggregated form of a β-amyloid peptide claim 1 , wherein the said antibody binds to an epitope on Aβthat includes amino acids 25-34 and 40 claim 1 , wherein said antibody binds to Aβwith higher affinity than its binding to Aβand Aβ claim 1 , wherein said antibody binds to Aβwith a Kof less than 1 μM.7. The method of claim 6 , wherein the antibody comprises a Fab fragment which binds Aβwith an affinity of about 10 nM or less.8. The method of claim 6 , wherein the antibody prevents claim 6 , treats claim 6 , inhibits or delays development of a disease ...

Anti-NGF antibodies and methods using same

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

PCSK9 ANTAGONISTS

The present invention provides antagonizing antibodies, antigen-binding portions thereof, and aptamers that bind to proprotein convertase subtilisin kexin type 9 (PCSK9). Also provided are antibodies directed to peptides, in which the antibodies bind to PCSK9. The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acid. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof to reduce LDL-cholesterol levels and/or for the treatment and/or prevention of cardiovascular disease, including treatment of hypercholesterolemia.

STABILITY-MODULATING LINKERS FOR USE WITH ANTIBODY DRUG CONJUGATES

The present invention provides stability-modulated antibody-drug conjugates, stability-modulating linker components used to make these stability-modulated antibody-drug conjugates, therapeutic methods using stability-modulated antibody-drug conjugates, and methods of making stability modulating linkers and stability-modulated antibody-drug conjugates.

PCSK9 ANTAGONISTS

The present invention provides antagonizing antibodies, antigen-binding portions thereof, and aptamers that bind to proprotein convertase subtilisin kexin type 9 (PCSK9). Also provided are antibodies directed to peptides, in which the antibodies bind to PCSK9. The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acid. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof to reduce LDL-cholesterol levels and/or for the treatment and/or prevention of cardiovascular disease, including treatment of hypercholesterolemia.

Methods for treating bone cancer pain by administering a nerve growth factor antagonist

The invention features methods and compositions for preventing or treating bone cancer pain including cancer pain associated with bone metastasis by administering an antagonist of nerve growth factor (NGF). The NGF antagonist may be an anti-NGF (such as anti-hNGF) antibody that is capable of binding hNGF.

Agonist anti-trkC antibodies and methods using same

The invention concerns agonist anti-trkC antibodies, polypeptides, and polynucleotides encoding the same. The invention further concerns use of such antibodies, polypeptides and/or polynucleotides in the treatment and/or prevention of neuropathies, such as sensory neuropathies, including taxol-induced sensory neuropathy, cisplatin-induced sensory neuropathy, and pyridoxine-induced sensory neuropathy.

ANTAGONIST ANTI-IL-7 RECEPTOR ANTIBODIES AND METHODS

The present invention provides antagonizing antibodies that bind to interleukin-7 receptor (IL-7R). The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acids. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof for the treatment and/or prevention of type 2 diabetes and immunological disorders, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, graft-versus-host disease, and lupus. 1. An isolated interleukin-7 receptor (IL-7R) antibody which specifically binds to interleukin-7 receptor alpha (IL-7Rα) and comprises an antigen binding region that cross-competes with a monoclonal antibody selected from the group consisting of P3A9 , P4B3 , P2D2 , P2E11 , HAL403a , HAL403b , C1GM and C2M3 , for binding to IL-7Rα.2. The antibody of claim 1 , wherein the antibody binds to an epitope comprising residues I82 claim 1 , K84 claim 1 , K100 claim 1 , T105 claim 1 , and Y192 of human IL-7Rα.3. An isolated antibody which specifically binds to interleukin-7 receptor alpha (IL-7Rα) claim 1 , wherein the antibody comprises a heavy chain variable region (VH) complementary determining region one (CDR1) having the amino acid sequence XXVMH claim 1 , wherein Xis D or N; Xis S or Y (SEQ ID NO: 50) claim 1 , a VH CDR2 having the amino acid sequence XXXXXGXXTYYADSVKG claim 1 , wherein Xis L or A; Xis V or I; Xis G or S claim 1 , Xis W or G claim 1 , Xis D or S claim 1 , Xis F claim 1 , G or S claim 1 , Xis F claim 1 , A or S (SEQ ID NO: 51) claim 1 , and a VH CDR3 having the amino acid sequence XXXXXXXX claim 1 , wherein Xis Q or D; Xis G or I; Xis D or S claim 1 , Xis Y or G claim 1 , Xis M claim 1 , V or G; Xis G or F; Xis N claim 1 , D or M; Xis N claim 1 , Y or D (SEQ ID NO: 52) claim 1 , a light chain variable region (VL) CDR1 having the amino acid sequence TXSSGXIXSSYVQ wherein Xis R or G; Xis S or R Xis D or A (SEQ ID NO: 53) claim 1 , a VL CDR2 having ...

Anti-glucagon receptor antibodies and pharmaceutical compositions thereof

The present invention provides antagonizing antibodies that bind to glucagon receptor and methods of using same. The anti-glucagon receptor antibodies can be used therapeutically to lower glucose levels in blood, and can be in the prevention and/or treatment of glucose-related disorders, including diabetes, hyperglycemia, hyperinsulinemia, impaired fasting glucose, impaired glucose tolerance, dyslipidemia, or metabolic syndrome.

ANTIBODIES SPECIFIC FOR DKK-1 AND THEIR USES

The present invention provides antibodies and fragments thereof that bind to Dkk-1 and, in particular, to humanized antibodies and fragments thereof that bind to Dkk-1 and, even more particularly to fully humanized antibodies and immunologically functional fragments that bind to Dkk-1. Also provided are antibodies and fragments thereof which compete with the binding of an anti-mouse Dkk-1 monoclonal antibody for binding to Dkk-1+ cells. Also provided are nucleic acids encoding anti-Dkk-1 antibodies or fragments thereof, as well as expression vectors and host cells incorporating these nucleic acids for the recombinant expression of anti-Dkk-1 antibodies and fragments thereof. Also provided are methods of preparing the antibodies and fragments thereof of the invention. Also provided are bone anabolic agents. Pharmaceutical compositions comprising the antibodies or fragments thereof of the invention are also provided. Further provided are methods of treating diseases, conditions and disorders ...

Methods for treating osteoarthritis pain by administering a nerve growth factor antagonist and compositions containing the same

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Methods for treating taxol-induced gut disorder

This invention relates to the field of taxol-induced gut disorder. More specifically, the invention relates to methods of treating taxol-induced gut disorder comprising administration of agonist anti-trkC antibody for the treatment, prevention, and/or amelioration of a symptom of taxol-induced gut disorder.

VERFAHREN ZUR BEHANDLUNG VON POSTOPERATIVEN SCHMERZEN DURCH VERABREICHUNG EINES ANTIKÖRPERS GEGEN NERVENWACHSTUMSFAKTOR UND DIESEN ENTHALTENDE ZUSAMMENSETZUNGEN

ANTIBODY-DRUG CONJUGATES WITH HIGH DRUG LOADING

ENGINEERED POLYPEPTIDE CONJUGATES USING TRANSGLUTAMINASE

The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates) comprising specific acyl donor glutamine-containing tags and amine donor agents. The invention also provides methods of making such engineered polypeptide conjugates using transglutaminase and methods of using thereof. 128-. (canceled)29. A method of treating a cancer in a subject in need thereof , comprising administering to the subject an effective amount of an engineered polypeptide conjugate comprising the formula: polypeptide-T-A , wherein T is an acyl donor glutamine-containing tag engineered at a specific site , wherein A is an amine donor agent , wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag at a carboxyl terminus , an amino terminus , or at an another site in the polypeptide , and wherein the acyl donor glutamine-containing tag comprises an amino acid sequence GGLLQGPP (SEQ ID NO:13).30. A method of treating a cancer in a subject in need thereof , comprising administering to the subject an effective amount of an engineered Fc-containing polypeptide conjugate comprising the formula: (Fc-containing polypeptide-T-A) , wherein T is an acyl donor glutamine-containing tag engineered at a specific site , wherein A is an amine donor agent , wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag at a carboxyl terminus , an amino terminus , or at an another site in the Fc-containing polypeptide , wherein the acyl donor glutamine-containing tag comprises an amino acid sequence XXQX (SEQ ID NO:35) , LLQ , or GLLQ (SEQ ID NO: 24) , wherein X is any amino acid , and wherein the engineered Fc-containing polypeptide conjugate comprises an amino acid substitution from glutamine to asparagine at position 295 (Q295N; EU numbering scheme).31. The method of claim 30 , wherein the acyl donor glutamine-containing tag comprises an amino acid sequence selected from the group ...

Pcsk9 antagonists

ENGINEERED POLYPEPTIDE CONJUGATES USING TRANSGLUTAMINASE

The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates) comprising specific acyl donor glutamine-containing tags and amine donor agents. The invention also provides methods of making such engineered polypeptide conjugates using transglutaminase and methods of using thereof. 122-. (canceled)23. A method for preparing an engineered polypeptide conjugate comprising the formula: polypeptide-T-A , wherein T is an acyl donor glutamine-containing tag engineered at a specific site , wherein A is an amine donor agent , wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag at a carboxyl terminus , an amino terminus , or at an another site in the polypeptide , and wherein the acyl donor glutamine-containing tag comprises an amino acid sequence LLQGPX , wherein X is A or P (SEQ ID NO:14) , or GGLLQGPP (SEQ ID NO:13) , comprising the steps of:a) providing an engineered polypeptide-T molecule comprising the Fc-containing polypeptide and the acyl donor glutamine-containing tag;b) contacting the amine donor agent with the engineered polypeptide-T molecule in the presence of a transglutaminase; andc) allowing the engineered polypeptide-T to covalently link to the amine donor agent to form the engineered Fc-containing polypeptide conjugate.24. The method of claim 23 , wherein the engineered polypeptide conjugate has conjugation efficiency of at least about 51%.25. The method of claim 23 , wherein the transglutaminase is a microbial claim 23 , purified claim 23 , or engineered transglutaminase.26. The method of claim 23 , further comprising a purification step claim 23 , wherein the engineered polypeptide conjugate is purified by a chromatography step.27. The method claim 23 , wherein the engineered polypeptide-T molecule is expressed in CHO cells.28. The method of claim 23 , wherein the polypeptide is Fc-containing or Fab-containing polypeptide. This application claims the benefits of U.S. ...

Antibodies specific for DKK-1 and their uses

The present invention provides antibodies and fragments thereof that bind to Dkk-1 and, in particular, to humanized antibodies and fragments thereof that bind to Dkk-1 and, even more particularly to fully humanized antibodies and immunologically functional fragments that bind to Dkk-1. Also provided are antibodies and fragments thereof which compete with the binding of an anti-mouse Dkk-1 monoclonal antibody for binding to Dkk-1+ cells. Also provided are nucleic acids encoding anti-Dkk-1 antibodies or fragments thereof, as well as expression vectors and host cells incorporating these nucleic acids for the recombinant expression of anti-Dkk-1 antibodies and fragments thereof. Also provided are methods of preparing the antibodies and fragments thereof of the invention. Also provided are bone anabolic agents. Pharmaceutical compositions comprising the antibodies or fragments thereof of the invention are also provided. Further provided are methods of treating diseases, conditions and disorders ...

METHODS FOR TREATING BONE CANCER PAIN BY ADMINISTERING A NERVE GROWTH FACTOR ANTAGONISTIC ANTIBODY

Methods for treating post-surgical pain by administering an anti-nerve growth factor antagonist antibody

The invention features methods and compositions for preventing or treating post-surgical pain by administering an anti-NGF antagonist antibody.

Anti-IL-7 receptor antibodies

The present invention provides antagonizing antibodies that bind to interleukin-7 receptor (IL-7R). The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acids. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof for the treatment and/or prevention of type 2 diabetes and immunological disorders, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, graft-versus-host disease, and lupus.

VERFAHREN ZUR BEHANDLUNG VON SCHMERZEN DURCH VERABREICHUNG EINES NERVENWACHSTUMSFAKTOR-ANTAGONISTEN UND EINES NSAID UND DIESE ENTHALTENDE ZUSAMMENSETZUNG

Antibodies directed against amyloid-beta peptide

Monoclonal antibody 9TL and antibodies derived from 9TL directed against amyloid-beta peptide and methods of using same for diagnosing and treatment of Alzheimer's disease and A peptide associated diseases are described. Methods of using antibodies directed against amyloid-beta peptide having impaired effector function for treatment of Alzheimer's disease and A peptide associated diseases are also described.

Heterodimeric proteins and methods for producing and purifying them

The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and other heterodimeric proteins comprising immunoglobulin-like hinge sequences. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided.

Engineered polypeptide conjugates and methods for making thereof using transglutaminase

The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates, toxin-(biocompatible polymer) conjugates, antibody-(biocompatible polymer) conjugates, and bispecific antibodies) comprising acyl donor glutamine-containing tags and amine donor agents. In one aspect, the invention provides an engineered Fc-containing polypeptide conjugate comprising the formula (Fc-containing polypeptide)-T-A, wherein T is an acyl donor glutamine-containing tag engineered at a specific site or comprises an endogenous glutamine made reactive by the Fc-containing polypeptide engineering, wherein A is an amine donor agent, and wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag or the endogenous glutamine. The invention also provides methods of making engineered polypeptide conjugates using transglutaminase.

ENGINEERED POLYPEPTIDE CONJUGATES AND METHODS FOR MAKING THEREOF USING TRANSGLUTAMINASE

The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates, toxin-(biocompatible polymer) conjugates, antibody-(biocompatible polymer) conjugates, and bispecific antibodies) comprising acyl donor glutamine-containing tags and amine donor agents. In one aspect, the invention provides an engineered Fc-containing polypeptide conjugate comprising the formula (Fc-containing polypeptide)-T-A, wherein T is an acyl donor glutamine-containing tag engineered at a specific site or comprises an endogenous glutamine made reactive by the Fc-containing polypeptide engineering, wherein A is an amine donor agent, and wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag or the endogenous glutamine. The invention also provides methods of making engineered polypeptide conjugates using transglutaminase.

Antibodies specific for TROP-2 and their uses

The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer.

Anti-PD-1 antibodies and methods of use thereof

The present invention provides antagonizing antibodies that bind to programmed cell death protein 1 (PD-1) and methods of using same. The anti-PD-1 antibodies can be used therapeutically alone or in combination with other therapeutics to treat cancer and other diseases.

ANTAGONIST ANTI-IL-7 RECEPTOR ANTIBODIES AND METHODS

The present invention provides antagonizing antibodies that bind to interleukin-7 receptor (IL-7R). The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acids. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof for the treatment and/or prevention of type 2 diabetes and immunological disorders, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, graft-versus-host disease, and lupus.

Method for reducing a level of LDL-cholesterol by an antibody that specifically binds to PCSK9

The present invention provides antagonizing antibodies, antigen-binding portions thereof, and aptamers that bind to proprotein convertase subtilisin kexin type 9 (PCSK9). Also provided are antibodies directed to peptides, in which the antibodies bind to PCSK9. The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acid. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof to reduce LDL-cholesterol levels and/or for the treatment and/or prevention of cardiovascular disease, including treatment of hypercholesterolemia.

Methods for treating pain by administering a nerve growth factor antagonist and an NSAID and compositions containing the same

The present invention features methods for treating or preventing pain comprising administering an amount of a nerve growth factor antagonist (such as an anti-NGF antibody) and an amount of an NSAID such that together they provide effective pain relief. The invention also features compositions comprising a nerve growth factor antagonist and an NSAID and kits containing the same.

Use of antibodies directed against amyloid-beta peptide for the treatment of age-related macular degeneration

Polynucleotides encoding antibodies directed against amyloid-beta peptide

Monoclonal antibody 9TL and antibodies derived from 9TL directed against amyloid-beta peptide and methods of using same for diagnosing and treatment of Alzheimer's disease and A peptide associated diseases are described. Methods of using antibodies directed against amyloid-beta peptide having impaired effector function for treatment of Alzheimer's disease and A peptide associated diseases are also described.

ANTI-NGF ANTIBODIES AND METHODS USING SAME

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain. 133-. (canceled)34. A method for treating post-herpetic neuralgia in an individual comprising administering an effective amount of a monoclonal anti-NGF antagonist antibody to an individual suffering from post-herpetic neuralgia , thereby treating post-herpetic neuralgia in said individual.35. The method of claim 34 , wherein the antibody is administered at a dosing frequency in a range from once every week to once every twelve weeks.36. The method of claim 34 , wherein the antibody is administered once every month claim 34 , once every two months claim 34 , once every three months claim 34 , once every four months claim 34 , once every five months claim 34 , or once every six months.37. The method of claim 34 , wherein the antibody is administered once every three months.38. The method of claim 34 , wherein the antibody is administered at a dose in a range from about 3 μg/kg to about 1 mg/kg.39. The method of claim 34 , wherein the antibody is administered at a dose of about 100 μg/kg.40. The method of claim 34 , wherein the antibody is administered at a dose of about 300 μg/kg.41. The method of claim 34 , wherein the antibody is administered intravenously or subcutaneously.42. The method of claim 34 , wherein the antibody is a humanized antibody or a human antibody.43. The method of claim 34 , wherein the antibody (a) blocks the interaction of human NGF with p75 and trkA claim 34 , (b) binds human NGF with a Kof less than about 2 nM claim 34 , and (c) blocks human NGF-dependent neuron survival.44. The method of claim 34 , wherein the antibody comprises a heavy chain variable region (VH) comprising three CDRs of the sequence shown in SEQ ID NO: ...

Antibodies specific for dkk-1 and their uses

STABILITY-MODULATING LINKERS FOR USE WITH ANTIBODY DRUG CONJUGATES

The present invention provides stability-modulated antibody-drug conjugates, stability-modulating linker components used to make these stability-modulated antibody-drug conjugates, therapeutic methods using stability-modulated antibody-drug conjugates, and methods of making stability modulating linkers and stability-modulated antibody-drug conjugates.

Methods of Treating Alzheimer's Disease Using Antibodies Directed Against Amyloid Beta Peptide and Compositions Thereof

Monoclonal antibodies directed against amyloid beta peptide and methods of using same for treatment and prevention of Alzheimer's disease and Down's syndrome are described.

ANTIBODIES DIRECTED AGAINST AMYLOID-BETA PEPTIDE AND METHODS USING SAME

Monoclonal antibody 9TL and antibodies derived from 9TL directed ag st amyloid-beta peptide and methods of using same for diagnosing and treatm of Alzheimer's disease and amyloid-beta peptide associated diseases are de ribed. Methods of using antibodies directed against amyloid-beta peptide havin mpaired effector function for treatment of Alzheimer's disease and amyloid-b a peptide associated diseases are also described.(no suitable figure) ANTIBODIES DIRECTED AGAINST AMYLOID-BETA PEPTIDE AND METHODS USING SAMEAbstractMonoclonal antibody 9TL and antibodies derived from 9TL directed against amyloid-beta peptide and methods of using same for diagnosing and treatment of Alzheimer's disease and amyloid-beta peptide associated diseases are described. Methods of using antibodies directed against amyloid-beta peptide having impaired effector function for treatment of Alzheimer's disease and amyloid-beta peptide associated diseases are also described.(no suitable figure) ...

Antibodies with pH Dependent Antigen Binding

The present invention relates to antibodies with pH dependent binding to its antigen such that the affinity for antigen binding at physiological pH (i.e., pH 7.4) is greater than at endosomal pH (i.e., pH 6.0 or 5.5). In other words, the KD or koff ratio at pH 5.5/pH 7.4 or at pH 6.0/pH 7.4 is more than, or ranges between, 2, 3, 4, 8, 10, 16, 20, 30, 40, or 100 or more. Such pH dependent antibodies preferentially dissociate from the antigen in the endosome. This can increase antibody half life, as compared to antibodies with equivalent KDs at pH 7.4 but with no pH dependent binding, when the antigen is one that undergoes antigen-mediated clearance (e.g., PCSK9). Antibodies with pH dependent binding can decrease total antigen half life when the antigen undergoes reduced clearance when bound to antibody (e.g., IL6). Antibodies with pH dependent binding can also prolong the decrease in antigen which is not antibody-bound. This can be important when antagonizing a target antigen typically present ...

Anti-NGF antibodies and methods using same

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Antibodies specific for trop-2 and their uses

The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer.

HETERODIMERIC PROTEINS AND METHODS FOR PRODUCING AND PURIFYING THEM

The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and other heterodimeric proteins comprising immunoglubulin-like hinge sequences. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided. 172-. (canceled)73. A heterodimeric protein comprising:{'figref': [{'@idref': 'DRAWINGS', 'FIG. 6A'}, {'@idref': 'DRAWINGS', 'FIG. 10'}], 'a hinge region comprising a first immunoglobulin-like hinge polypeptide and a second immunoglobulin-like hinge polypeptide which interact together to form a dimeric hinge interface, wherein electrostatic interactions between one or more charged amino acids within the hinge interface favor interaction between the first and second hinge polypeptides over interaction between two first hinge polypeptides or two second hinge polypeptides, thereby promoting heterodimer formation over homodimer formation, wherein the hinge region is a human IgG1 hinge region, wherein the first hinge polypeptide comprises at least one amino acid modification relative to a wild-type IgG hinge region; wherein the wild-type amino acid in the first hinge polypeptide is replaced with an amino acid having an opposite charge to the corresponding amino acid in the second hinge polypeptide, wherein the amino acid modification in the hinge region is at a position selected from the group consisting of Asp221 and Pro228 as shown at , and further comprising an immunoglobulin-like CH3 region comprising a first CH3 polypeptide fused to the first hinge polypeptide and a second CH3 polypeptide fused to the second hinge polypeptide, wherein the first CH3 polypeptide and the second CH3 polypeptide comprise at least one amino acid modification relative to a wild-type IgG1 CH3 region sequence at a position selected from the group consisting of Tyr349, Leu368, Phe405, and ...

Methods for treating osteoarthritis pain by administering a nerve growth factor antagonist and compositions containing the same

ANTI-PD-1 ANTIBODIES AND METHODS OF USE THEREOF

The present invention provides antagonizing antibodies that bind to programmed cell death protein 1 (PD-1) and methods of using same. The anti-PD-1 antibodies can be used therapeutically alone or in combination with other therapeutics to treat cancer and other diseases. 128-. (canceled)29. A method for treating cancer in a subject in need thereof , the method comprising administering to the individual an effective amount of an antagonist antibody that specifically binds to programmed cell death 1 (PD-1) and comprises:a heavy chain variable region (VH) comprising a VH complementarity determining region one (CDR1), VH CDR2, and VH CDR3 of the VH having an amino acid sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6; anda light chain variable region (VL) comprising a VL CDR1, VL CDR2, and VL CDR3 of the VL having an amino acid sequence selected from the group consisting of SEQ ID NO: 2, SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9,such that one or more symptoms associated with the cancer is ameliorated in the individual.30. The method of claim 29 , wherein the cancer is selected from the group consisting of gastric cancer claim 29 , sarcoma claim 29 , lymphoma claim 29 , Hodgkin's lymphoma claim 29 , leukemia claim 29 , head and neck cancer claim 29 , squamous cell head and neck cancer claim 29 , thymic cancer claim 29 , epithelial cancer claim 29 , salivary cancer claim 29 , liver cancer claim 29 , stomach cancer claim 29 , thyroid cancer claim 29 , lung cancer claim 29 , ovarian cancer claim 29 , breast cancer claim 29 , prostate cancer claim 29 , esophageal cancer claim 29 , pancreatic cancer claim 29 , glioma claim 29 , leukemia claim 29 , multiple myeloma claim 29 , renal cell carcinoma claim 29 , bladder cancer claim 29 , cervical cancer claim 29 , choriocarcinoma claim 29 , colon cancer claim 29 , oral cancer claim 29 , skin cancer claim 29 , and melanoma.31. The method of claim 29 , wherein the individual ...

Methods for treating post-surgical pain by administering an anti-nerve growth factor antagonist

The invention features methods and compositions for preventing or treating pain resulting from surgery or an incision by administering an antagonist of nerve growth factor (NGF). The NGF antagonist may be an anti-NGF (such as anti-hNGF) antibody that is capable of binding hNGF.

Methods for treating osteoarthritis pain by administering a nerve growth factor antagonist and compositions containing the same

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

ANTIBODY-DRUG CONJUGATES WITH HIGH DRUG LOADING

The present invention provides transglutaminase-mediated antibody-drug conjugates with high anti-body-drug ratio (DAR) comprising 1) glutamine-containing tags, endogenous glutamines, and/or endogenous glutamines made reactive by antibody engineering or an engineered transglutaminase (e.g., with altered substrate specifity); and 2) amine donor agents comprising amine donor units, linkers, and agent moieties, wherein the DAR is at least about 5. The invention also provides methods of making and methods of using such higher drug loaded antibody-drug conjugates.

METHODS FOR TREATING OSTEOARTHITIS PAIN BY ADMINISTERING A NERVE GROWTH FACTOR ANTAGONIST AND COMPOSITIONS CONTAINING THE SAME

Method of treating type 1 diabetes with antagonist IL-7 receptor antibodies

The present invention provides antagonizing antibodies that bind to interleukin-7 receptor (IL-7R). The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acids. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof for the treatment and/or prevention of type 2 diabetes and immunological disorders, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, graft-versus-host disease, and lupus.

Antibodies specific for Trop-2 and their uses

The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer.

Engineered polypeptide conjugates using transglutaminase

The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates) comprising specific acyl donor glutamine-containing tags and amine donor agents. The invention also provides methods of making such engineered polypeptide conjugates using transglutaminase and methods of using thereof.

Antibodies specific for Trop-2 and their uses

The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer.

Anti-PD-1 antibodies and methods of use thereof

The present invention provides antagonizing antibodies that bind to programmed cell death protein 1 (PD-1) and methods of using same. The anti-PD-1 antibodies can be used therapeutically alone or in combination with other therapeutics to treat cancer and other diseases.

Methods for treating bone cancer by administering a nerve growth factor antagonist antibody

The invention features methods and compositions for preventing or treating bone cancer pain including cancer pain associated with bone metastasis by administering an antagonist of nerve growth factor (NGF). The NGF antagonist may be an anti-NGF (such as anti-hNGF) antibody that is capable of binding hNGF.

Anti-pd-1 antibodies and methods of use thereof

Antibodies specific for trop-2 and their uses

TREATMENT WITH ANTI-EFNA4 ANTIBODY-DRUG CONJUGATES

The present invention provides for dosing regimens for the treatment of patients with cancer and/or an EFNA4-associated disorder with an anti-EFNA4 antibody-drug conjugate (ADC). The present invention further provides for methods for the treatment of patients with cancer and/or an EFNA4-associated disorder in which an anti-EFNA4 ADC is administered intravenously weekly (QW) or every 3 weeks (Q3W).

Heterodimeric proteins and methods for producing and purifying them

The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and other heterodimeric proteins comprising immunoglobulin-like hinge sequences. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided.

METHODS FOR TREATING BONE CANCER PAIN BY ADMINISTERING A NERVE GROWTH FACTOR ANTAGONIST

METHODS FOR TREATING OSTEOARTHRITIS PAIN BY ADMINISTERING A NERVE GROWTH FACTOR ANTAGONIST AND COMPOSITIONS CONTAINING THE SAME

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain. 185-. (canceled)86. A method for treating osteoarthritis pain comprising administering an effective amount of a monoclonal anti-NGF antagonist antibody to an individual having osteoarthritis , thereby treating osteoarthritis pain in said individual.87. The method of claim 86 , wherein the antibody is administered at a dosing frequency in a range from once every week to once every twelve weeks.88. The method of claim 86 , wherein the antibody is administered once every month claim 86 , once every two months claim 86 , once every three months claim 86 , once every four months claim 86 , once every five months claim 86 , or once every six months.89. The method of claim 86 , wherein the antibody is administered once every three months.90. The method of claim 86 , wherein the antibody is administered at a dose in a range from about 3 μg/kg to about 1 mg/kg.91. The method of claim 86 , wherein the antibody is administered at a dose of about 100 μg/kg.92. The method of claim 86 , wherein the antibody is administered at a dose of about 300 μg/kg.93. The method of claim 86 , wherein the antibody is administered intravenously or subcutaneously.94. The method of claim 86 , wherein the antibody is a humanized antibody or a human antibody.95. The method of claim 86 , wherein the antibody (a) blocks the interaction of human NGF with p75 and trkA claim 86 , (b) binds human NGF with a Kof less than about 2 nM claim 86 , and (c) blocks human NGF-dependent neuron survival claim 86 , thereby treating osteoarthritis pain in the individual.96. The method of claim 86 , wherein the antibody comprises a heavy chain variable region (VH) comprising three CDRs of the ...

Methods for treating bone cancer pain by administering a nerve growth factor antagonist

HETERODIMERIC PROTEINS AND METHODS FOR PRODUCING AND PURIFYING THEM

The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and other heterodimeric proteins comprising immunoglobulin-like hinge sequences. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided. 152-. (canceled)53. A cell line expressing a heterodimeric protein , wherein the heterodimeric protein comprises:{'figref': [{'@idref': 'DRAWINGS', 'FIG. 6A'}, {'@idref': 'DRAWINGS', 'FIG. 10'}], 'a hinge region comprising a first immunoglobulin-like hinge polypeptide and a second immunoglobulin-like hinge polypeptide which interact together to form a dimeric hinge interface, wherein electrostatic interactions between one or more charged amino acids within the hinge interface favor interaction between the first and second hinge polypeptides over interaction between two first hinge polypeptides or two second hinge polypeptides, thereby promoting heterodimer formation over homodimer formation, wherein the hinge region is a human IgG1 or IgG2 hinge region, wherein the first hinge polypeptide comprises at least one amino acid modification relative to a wild-type IgG hinge region; wherein the wild-type amino acid in the first hinge polypeptide is replaced with an amino acid having an opposite charge to the corresponding amino acid in the second hinge polypeptide, wherein the amino acid modification in the hinge region is at a position selected from the group consisting of 1) Asp221 or 2) Cys223 and/or Glu225 as shown at , and further comprising an immunoglobulin-like CH3 region comprising a first CH3 polypeptide fused to the first hinge polypeptide and a second CH3 polypeptide fused to the second hinge polypeptide, wherein the first CH3 polypeptide and the second CH3 polypeptide comprise at least one amino acid modification relative to a wild-type IgG1 CH3 region ...

Methods for treating osteoarthritis pain by administering a nerve growth factor antagonist and compositions containing the same

Antibodies directed against amyloid-beta peptide and methods using same

Anti-PCSK9 antibodies with pH dependent antigen binding

The present invention relates to antibodies with pH dependent binding to its antigen such that the affinity for antigen binding at physiological pH (i.e., pH 7.4) is greater than at endosomal pH (i.e., pH 6.0 or 5.5). In other words, the KD or koff ratio at pH 5.5/pH 7.4 or at pH 6.0/pH 7.4 is more than, or ranges between, 2, 3, 4, 8, 10, 16, 20, 30, 40, or 100 or more. Such pH dependent antibodies preferentially dissociate from the antigen in the endosome. This can increase antibody half life, as compared to antibodies with equivalent KDs at pH 7.4 but with no pH dependent binding, when the antigen is one that undergoes antigen-mediated clearance (e.g., PCSK9). Antibodies with pH dependent binding can decrease total antigen half life when the antigen undergoes reduced clearance when bound to antibody (e.g., IL6). Antibodies with pH dependent binding can also prolong the decrease in antigen which is not antibody-bound. This can be important when antagonizing a target antigen typically present ...

METHODS FOR TREATING POST-SURGICAL PAIN BY ADMISNISTERING AN ANTIBODY AGAINST NERVE GROWTH FACTOR AND COMPOSITIONS CONTAINING THE SAME

PC33718E

The present invention provides antagonizing antibodies, antigen-binding portions thereof, and aptamers that bind to proprotein convertase subtilisin kexin type 9 (PCSK9). Also provided are antibodies directed to peptides, in which the antibodies bind to PCSK9. The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acid. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof to reduce LDL-cholesterol levels and/or for the treatment and/or prevention of cardiovascular disease, including treatment of hypercholesterolemia.

ANTI-NGF ANTIBODIES AND METHODS USING SAME

POLYNUCLEOTIDES ENCODING ANTIBODIES DIRECTED AGAINST AMYLOID-BETA PEPTIDE

Monoclonal antibody 9TL and antibodies derived from 9TL directed against amyloid-beta peptide and methods of using same for diagnosing and treatment of Alzheimer's disease and Aβ peptide associated diseases are described. Methods of using antibodies directed against amyloid-beta peptide having impaired effector function for treatment of Alzheimer's disease and Aβ peptide associated diseases are also described.

Antibodies directed against amyloid-beta peptide and methods using same

Monoclonal antibody 9TL and antibodies derived from 9TL directed against amyloid-beta peptide and methods of using same for diagnosing and treatment of Alzheimer's disease and A peptide associated diseases are described. Methods of using antibodies directed against amyloid-beta peptide having impaired effector function for treatment of Alzheimer's disease and A peptide associated diseases are also described.

Antibodies directed against amyloid-beta peptide and methods using same

Monoclonal antibody 9TL and antibodies derived from 9TL directed against amyloid-beta peptide and methods of using same for diagnosing and treatment of Alzheimer's disease and Aβ peptide associated diseases are described. Methods of using antibodies directed against amyloid-beta peptide having impaired effector function for treatment of Alzheimer's disease and Aβ peptide associated diseases are also described.

HETERODIMERIC PROTEINS AND METHODS FOR PRODUCING AND PURIFYING THEM

The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and other heterodimeric proteins comprising immunoglobulin-like hinge sequences. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided. 1. A heterodimeric protein comprising:a hinge region comprising a first immunoglobulin-like hinge polypeptide and a second immunoglobulin-like hinge polypeptide which interact together to form a dimeric hinge interface, wherein electrostatic interactions between one or more charged amino acids within the hinge interface favor interaction between the first and second hinge polypeptides over interaction between two first hinge polypeptides or two second hinge polypeptides, thereby promoting heterodimer formation over homodimer formation.2. The heterodimeric protein of claim 1 , wherein the hinge region is an IgG hinge region.3. (canceled)4. The heterodimeric protein of claim 2 , wherein the first hinge polypeptide comprises at least one amino acid modification relative to a wild-type IgG hinge region; and the second hinge polypeptide comprises at least one amino acid modification relative to a wild-type IgG hinge region at the same position as the amino acid modification in the first hinge polypeptide claim 2 , wherein the wild-type amino acid in the second hinge polypeptide is replaced with an amino acid having an opposite charge to the corresponding amino acid modification in the first hinge polypeptide.5. The heterodimeric protein of claim 4 , wherein the amino acid modifications are selected from the group consisting of Lys claim 4 , Arg claim 4 , Asp claim 4 , and Glu.6. The heterodimeric protein of claim 4 , wherein the IgG hinge region comprises a human IgG hinge region.7. The heterodimeric protein of claim 6 , wherein the human IgG hinge region comprises a ...

Antibodies specific for trop-2 and their uses

The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer.

ANTIBODIES SPECIFIC FOR TROP-2 AND THEIR USES

The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer. 1. An isolated polynucleotide comprising a nucleotide sequence encoding an antibody which specifically binds to Trop-2 , wherein the antibody comprises{'sub': 1', '2', '1', '2', 'i', '1', '1', '1, '(a) a heavy chain variable (VH) region comprising (i) a VH complementarity determining region one (CDR1) comprising the sequence SYWIN (SEQ ID NO: 40), GYTFTSY (SEQ ID NO: 41), or GYTFTSYWIN (SEQ ID NO: 42); (ii) a VH CDR2 comprising the sequence NIXPSDSYSNYNXKFKD wherein Xis Y or F; Xis Q or K (SEQ ID NO: 51), or XPSDSY wherein Xis Y or F (SEQ ID NO: 52); and iii) a VH CDR3 comprising the sequence GSXFDY wherein Xis S or G (SEQ ID NO: 53); and'}{'sub': 1', '2', '1', '2, '(b) a light chain variable region (VL) region comprising (i) a VL CDR1 comprising the sequence RASQTIGTSIH (SEQ ID NO: 59); (ii) a VL CDR2 comprising the sequence YASESIS (SEQ ID NO: 60); and (iii) a VL CDR3 comprising the sequence XQSXSWPFT wherein Xis Q or S; Xis N or F (SEQ ID NO:64).'}2. An isolated polynucleotide comprising a nucleotide sequence encoding an antibody which specifically binds to Trop-2 , wherein the antibody comprises:a VH region comprising a VH CDR1, VH CDR2, and VH CDR3 of the VH sequence shown in SEQ ID NO: 13; anda VL region comprising VL CDR1, VL CDR2, and VL CDR3 of the VL sequence shown in SEQ ID NO: 12.3. The isolated polynucleotide of claim 2 , wherein the VH region comprises (i) a VH CDR1 comprising the sequence SYWIN (SEQ ID NO: 40) ...

ANTAGONIST ANTI-IL-7 RECEPTOR ANTIBODIES AND METHODS

The present invention provides antagonizing antibodies that bind to interleukin-7 receptor (IL-7R). The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acids. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof for the treatment and/or prevention of type 2 diabetes and immunological disorders, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, graft-versus-host disease, and lupus. 114-. (canceled)15. A method for treating and/or preventing an autoimmune disorder in an individual , the method comprising administering a therapeutically effective amount of an antagonist IL-7R antibody to an individual suffering from or at risk for an autoimmune disorder , thereby ameliorating and/or preventing one or more symptoms of the autoimmune disorder , wherein the antibody comprises:a heavy chain variable region (VH) comprising CDR1, CDR2, and CDR3 of the VH region comprising the amino acid sequence shown in SEQ ID NO: 40; anda light chain variable region (VL) comprising CDR1, CDR2, and CDR3 of the VL region comprising the amino acid sequence shown in SEQ ID NO: 41.16. The method of claim 15 , wherein administration of the antagonist IL-7R antibody results in reduced naïve and activated T cell populations in the individual compared to before administration.17. The method of claim 16 , wherein the reduced T cell populations in the individual comprise T1 and/or T17 cells.18. A method of treating and/or preventing type 2 diabetes in an individual claim 16 , the method comprising administering a therapeutically effective amount of an antagonist IL-7R antibody to an individual suffering from or at risk for type 2 diabetes claim 16 , thereby ameliorating and/or preventing one or more symptoms of type 2 diabetes claim 16 , wherein antibody comprises:a heavy chain variable region (VH) comprising CDR1, CDR2, and CDR3 of the VH region comprising the amino acid ...

ENGINEERED POLYPEPTIDE CONJUGATES USING TRANSGLUTAMINASE

The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates) comprising specific acyl donor glutamine-containing tags and amine donor agents. The invention also provides methods of making such engineered polypeptide conjugates using transglutaminase and methods of using thereof. 1. An engineered polypeptide conjugate comprising the formula: polypeptide-T-A , wherein T is an acyl donor glutamine-containing tag engineered at a specific site , wherein A is an amine donor agent , wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag at a carboxyl terminus , an amino terminus , or at an another site in the polypeptide , and wherein the acyl donor glutamine-containing tag comprises an amino acid sequence GGLLQGPP (SEQ ID NO:13).2. An engineered Fc-containing polypeptide conjugate comprising the formula: (Fc-containing polypeptide-T-A) , wherein T is an acyl donor glutamine-containing tag engineered at a specific site , wherein A is an amine donor agent , wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag at a carboxyl terminus , an amino terminus , or at an another site in the Fc-containing polypeptide , wherein the acyl donor glutamine-containing tag comprises an amino acid sequence XXQX (SEQ ID NO:35) , LLQ , or GLLQ (SEQ ID NO: 24) , wherein X is any amino acid , and wherein the engineered Fc-containing polypeptide conjugate comprises an amino acid substitution from glutamine to asparagine at position 295 (Q295N; EU numbering scheme).3. The engineered Fc-containing polypeptide conjugate of claim 2 , wherein the acyl donor glutamine-containing tag comprises an amino acid sequence selected from the group consisting of LLQGG (SEQ ID NO:16) claim 2 , LLQG (SEQ ID NO:17) claim 2 , LSLSQG (SEQ ID NO:18) claim 2 , GGGLLQGG (SEQ ID NO:19) claim 2 , GLLQG (SEQ ID NO:20) claim 2 , LLQ claim 2 , GSPLAQSHGG (SEQ ID NO:21) claim 2 , GLLQGGG ( ...

ANTAGONIST ANTI-IL-7 RECEPTOR ANTIBODIES AND METHODS

The present invention provides antagonizing antibodies that bind to interleukin-7 receptor (IL-7R). The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acids. The invention further relates to therapeutic methods for use of these antibodies and antigen-binding portions thereof for the treatment and/or prevention of type 2 diabetes and immunological disorders, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, graft-versus-host disease, and lupus. 1. An isolated interleukin-7 receptor (IL-7R) antibody which specifically binds to interleukin-7 receptor alpha (IL-7Rα) and comprises an antigen binding region that cross-competes with a monoclonal antibody selected from the group consisting of P3A9 , P4B3 , P2D2 , P2E11 , HAL403a , HAL403b , C1GM and C2M3 , for binding to IL-7Rα.2. The antibody of claim 1 , wherein the antibody binds to an epitope comprising residues I82 claim 1 , K84 claim 1 , K100 claim 1 , T105 claim 1 , and Y192 of human IL-7Rα.3. An isolated antibody which specifically binds to interleukin-7 receptor alpha (IL-7Rα) claim 1 , wherein the antibody comprises a heavy chain variable region (VH) complementary determining region one (CDR1) having the amino acid sequence XXVMH claim 1 , wherein Xis D or N; Xis S or Y (SEQ ID NO: 50) claim 1 , a VH CDR2 having the amino acid sequence XXXXXGXXTYYADSVKG claim 1 , wherein Xis L or A; Xis V or I; Xis G or S; Xis W or G; Xis D or S; Xis F claim 1 , G or S; Xis F claim 1 , A or S (SEQ ID NO: 51) claim 1 , and a VH CDR3 having the amino acid sequence XXXXXXXX claim 1 , wherein Xis Q or D; Xis G or I; Xis D or S; Xis Y or G; Xis M claim 1 , V or G; Xis G or F; Xis N claim 1 , D or M; Xis N claim 1 , Y or D (SEQ ID NO: 52) claim 1 , a light chain variable region (VL) CDR1 having the amino acid sequence TXSSGXIXSSYVQ wherein Xis R or G; Xis S or R; Xis D or A (SEQ ID NO: 53) claim 1 , a VL CDR2 having the amino acid sequence EDXQRPS wherein Xis D or N (SEQ ...

METHODS FOR REDUCING LDL-CHOLESTEROL

The present invention relates to methods for the treatment of reducing LDL-cholesterol levels in a subject infected with hepatitis C virus (HCV) or at high risk of contracting HCV comprising administration to the subject in need thereof a therapeutically effective amount of an antagonist antibody which specifically binds to a human PCSK9 protein. The subject treatment can be used in the prevention and/or treatment of cholesterol and lipoprotein metabolism disorders, including hypercholesterolemia, dyslipidemia, hyperlipidemia, atherosclerosis, acute coronary syndrome and, more generally, cardiovascular disease (CVD). 1. A method of reducing a level of LDL-cholesterol in blood of a subject infected with hepatitis C virus (HCV) or at high risk of contracting HCV , comprising administering to the subject in need thereof a therapeutically effective amount of an antagonist antibody which specifically binds to a human proprotein convertase subtilisin kexin type 9 (PCSK9) of SEQ ID NO:1.2. The method of claim 1 , wherein the antibody blocks LDLR binding to the PCSK9 of SEQ ID NO: 1.3. The method of claim 1 , wherein the antibody is alirocumab (PRALUENT™) claim 1 , evolocumab (REPATHA™) claim 1 , REGN728 claim 1 , LGT209 claim 1 , RG7652 claim 1 , LY3015014 claim 1 , L1L3 claim 1 , 31H4 claim 1 , 11F1 claim 1 , 12H11 claim 1 , 300N claim 1 , 8A1 claim 1 , 8A3 claim 1 , 3C4 claim 1 , or 1D05.4. The method of claim 1 , wherein the antibody comprises a heavy chain variable region (VH) comprising complementarity determining region one (CDR1) claim 1 , CDR2 claim 1 , and CDR3 of the amino acid sequence shown in SEQ ID NO: 2; and a light chain variable region (VL) comprising CDR1 claim 1 , CDR2 claim 1 , and CDR3 of the amino acid sequence shown in SEQ ID NO: 3.5. The method of claim 1 , wherein the antibody comprises a VH CDR1 having the amino acid sequence shown in SEQ ID NO: 4 claim 1 , 5 claim 1 , or 6 claim 1 , a VH CDR2 having the amino acid sequence shown in SEQ ID NO:7 or ...

Anti-glucagon receptor antibodies and methods of use thereof

The present invention provides antagonizing antibodies that bind to glucagon receptor and methods of using same. The anti-glucagon receptor antibodies can be used therapeutically to lower glucose levels in blood, and can be in the prevention and/or treatment of glucose-related disorders, including diabetes, hyperglycemia, hyperinsulinemia, impaired fasting glucose, impaired glucose tolerance, dyslipidemia, or metabolic syndrome.

Antibodies specific for trop-2 and their uses

The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer.

Methods of treating Alzheimer's disease using antibodies directed against amyloid beta peptide and compositions thereof

Monoclonal antibodies directed against amyloid beta peptide and methods of using same for treatment and prevention of Alzheimer's disease and Down's syndrome are described.

Engineered polypeptide conjugates and methods for making thereof using transglutaminase

The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates, toxin-(biocompatible polymer) conjugates, antibody-(biocompatible polymer) conjugates, and bispecific antibodies) comprising acyl donor glutamine-containing tags and amine donor agents. In one aspect, the invention provides an engineered Fc-containing polypeptide conjugate comprising the formula (Fc-containing polypeptide)-T-A, wherein T is an acyl donor glutamine-containing tag engineered at a specific site or comprises an endogenous glutamine made reactive by the Fc-containing polypeptide engineering, wherein A is an amine donor agent, and wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag or the endogenous glutamine. The invention also provides methods of making engineered polypeptide conjugates using transglutaminase.

Engineered polypeptide conjugates using transglutaminase

The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates) comprising specific acyl donor glutamine-containing tags and amine donor agents. The invention also provides methods of making such engineered polypeptide conjugates using transglutaminase and methods of using thereof.

Stability-modulating linkers for use with antibody-drug conjugates

Antibodies directed against amy-loid-beta peptide and methods using same

Antibodies directed against amyloid-beta peptide and methods using same

Antibodies specific for Trop-2 and their uses

本发明提供与滋养层细胞表面抗原2(Trop-2)特异性结合之抗体。本发明进一步提供包含抗体之抗体缀合物、编码抗体之核酸及获得抗体之方法。本发明还涉及使用这些抗体及Trop-2抗体缀合物以治疗与Trop-2表达有关之症状(例如癌，诸如结肠癌、食道癌、胃癌、头颈癌、肺癌、卵巢癌或胰癌)之治疗方法。

Antagonist anti-il-7 receptor antibodies and methods

本发明提供了结合白细胞介素-7受体(IL-7R)的拮抗性抗体。本发明进一步提供了获得这种抗体及抗体编码核酸的方法。本发明进一步涉及使用这些抗体及其抗原结合部分治疗和/或预防2型糖尿病和免疫疾病的治疗方法，所述免疫疾病包括1型糖尿病、多发性硬化、类风湿性关节炎、移植物抗宿主疾病及狼疮。

Anti-ngf antibodies and methods using same

ANTIBODIES WITH pH DEPENDENT ANTIGEN BINDING

The present invention relates to antibodies with pH dependent binding to its antigen such that the affinity for antigen binding at physiological pH (i.e., pH 7.4) is greater than at endosomal pH (i.e., pH 6.0 or 5.5). In other words, the K D or k off ratio at pH 5.5/ pH 7.4 or at pH 6.0/ pH 7.4 is more than, or ranges between, 2, 3, 4, 8, 10, 16, 20, 30, 40, or 100 or more. Such pH dependent antibodies preferentially dissociate from the antigen in the endosome. This can increase antibody half life, as compared to antibodies with equivalent K D s at pH 7.4 but with no pH dependent binding, when the antigen is one that undergoes antigen-mediated clearance (e.g., PCSK9). Antibodies with pH dependent binding can decrease total antigen half life when the antigen undergoes reduced clearance when bound to antibody (e.g., IL6). Antibodies with pH dependent binding can also prolong the decrease in antigen which is not antibody-bound. This can be important when antagonizing a target antigen typically present at high levels (e.g., IgE, DKK1, C5 and SOST). In addition, such antibodies can increase antigen half life when the antigen is a receptor and the receptor has increased clearance when bound to antibody (e.g, GMCSF receptor).

Methods for treating cardiac arrhythmia and preventing death due to cardiac arrhythmia using ngf antagonists

This invention relates to the field of cardiac disease. More specifically, the invention relates to methods using an NGF antagonist for treating and preventing cardiac arrhythmia and methods of preventing death due to cardiac arrhythmia.

Methods for treating post-surgical pain by administering an anti-nerve growth factor antagonist antibody and compositions containing the same

The invention features methods and compositions for preventing or treating post-surgical pain by administering an anti-NGF antagonist antibody.

Antibodies directed against amyloid-beta peptide and methods using same

Monoclonal antibody 9TL and antibodies derived from 9TL directed against amyloid-beta peptide and methods of using same for diagnosing and treatment of Alzheimer's disease and Aβ peptide associated diseases are described. Methods of using antibodies directed against amyloid-beta peptide having impaired effector function for treatment of Alzheimer's disease and Aβ peptide associated diseases are also described.

ANTIBODIES TARGETED AGAINST AMYLOID BETA PEPTIDE AND METHODS USING THEM

SE REFIERE A UN ANTICUERPO MONOCLONAL SELECCIONADO DE IgG1, IgG2; IgG3 E IgG4 EL CUAL SE UNE A UN PEPTIDO AB, ESPECIFICAMENTE A UN EPITOPO EN AB1-40 QUE INCLUYE LOS AMINOACIDOS 25-34 Y 40 CON UNA AFINIDAD DE APROXIMADAMENTE DE 5nM O MENOS. DICHO ANTICUERPO COMPRENDE UNA REGION VARIBLE DE CADENA PESADA SELECCIONADA DE SEQ ID NO:1, SEQ ID NO:3, SEQ ID NO:4 Y SEQ ID NO:5; Y UNA REGION VARIBLE DE CADENA LIGERA SELECCIONADA DE SEQ ID NO:2, SEQ ID NO:6, SEQ ID NO:7 Y SEQ ID NO:8. EL ANTICUERPO NO ES EL ANTICUERPO 2294. SON UTILES EN EL TRATAMIENTO DE ALZHEIMER REFERS TO A SELECTED MONOCLONAL ANTIBODY OF IgG1, IgG2; IgG3 AND IgG4 WHICH BIND WITH AN AB PEPTIDE, SPECIFICALLY TO AN EPITOPE AT AB1-40 INCLUDING AMINO ACIDS 25-34 AND 40 WITH AN AFFINITY OF APPROXIMATELY 5nM OR LESS. SAID ANTIBODY INCLUDES A HEAVY CHAIN VARIBLE REGION SELECTED FROM SEQ ID NO: 1, SEQ ID NO: 3, SEQ ID NO: 4 AND SEQ ID NO: 5; AND A VARIBLE REGION OF LIGHT CHAIN SELECTED FROM SEQ ID NO: 2, SEQ ID NO: 6, SEQ ID NO: 7 AND SEQ ID NO: 8. THE ANTIBODY IS NOT THE 2294 ANTIBODY. THEY ARE USEFUL IN THE TREATMENT OF ALZHEIMER

ANTI-BODIES ANTAGONISTS ANTI RECEIVER OF IL-7 AND PROCEDURES

La presente solicitud proporciona anticuerpos antagonizantes que se unen al receptor de interleucina 7 (IL-7R). La solicitud proporciona adicionalmente un procedimiento para obtener tales anticuerpos y ácidos nucleicos que codifican los anticuerpos. La solicitud se refiere adicionalmente a procedimientos terapéuticos para el uso de estos anticuerpos y partes de union a antígeno de los mismos para el tratamiento y/o la prevencion de diabetes tipo 2 y trastornos inmunologicos, incluyendo diabetes tipo 1, esclerosis multiple, artritis reumatoide, enfermedad de injerto contra huésped y lupus. Reivindicacion 1: Un anticuerpo del receptor de interleucina 7 (IL-7R) aislado que se une específicamente a IL-7R y comprende una region de union a antígeno que compite de forma cruzada, con un anticuerpo monoclonal seleccionado del grupo que consiste en P3A9, P4B3, P2D2, P2E11, HAL403a, HAL403b, C1GM y C2M3, por la union a IL-7R. The present application provides antagonizing antibodies that bind to the interleukin 7 receptor (IL-7R). The application further provides a method for obtaining such antibodies and nucleic acids encoding the antibodies. The application further relates to therapeutic procedures for the use of these antibodies and antigen binding parts thereof for the treatment and / or prevention of type 2 diabetes and immunological disorders, including type 1 diabetes, multiple sclerosis, rheumatoid arthritis, graft versus host disease and lupus. Claim 1: An isolated interleukin 7 (IL-7R) receptor antibody that specifically binds to IL-7R and comprises a cross-antigen-binding region with a monoclonal antibody selected from the group consisting of P3A9, P4B3, P2D2, P2E11, HAL403a, HAL403b, C1GM and C2M3, by joining IL-7R.

Staphylococcus aureus specific antibodies and uses thereof

The present invention provides antagonizing antibodies that bind to S. aureus alpha-toxin. The invention further provides a method of obtaining such antibodies and antibody encoding nucleic acids. The invention further relates to therapeutic methods for use of these antibodies for the treatment and/or prevention of staphylococcal disease, including, for example, pneumonia, bacteremia, sepsis, eye infection, and abscess.

Anti-glucagon receptor antibodies and methods of use thereof

The present invention provides antagonizing antibodies that bind to glucagon receptor and methods of using same. The anti-glucagon receptor antibodies can be used therapeutically to lower glucose levels in blood, and can be in the prevention and/or treatment of glucose-related disorders, including diabetes, hyperglycemia, hyperinsulinemia, impaired fasting glucose, impaired glucose tolerance, dyslipidemia, or metabolic syndrome.

Anti-sclerostin antibodies

The present disclosure provides antagonizing antibodies that specifically bind sclerostin. The disclosure further provides a method of obtaining such antibodies and antibody encoding nucleic acids. The disclosure further relates to therapeutic methods for use of these antibodies for the treatment and/or prevention of bone related disorders, including, for example, multiple myeloma, osteoporosis, osteopenia, Paget's Disease, bone fracture, or bone loss. Methods of increasing bone formation, bone mass, bone volume, bone mineralization, bone quality, bone strength, or bone density as well as methods of inducing canonical Wnt signaling activity and methods of preventing or reducing tumor burden, methods of inhibiting or preventing tumor growth or progression, methods of inhibiting metastasis of cancer cells or tumors or delaying tumor growth or progression are also provided.

Methods for reducing ldl-cholesterol

The present invention relates to methods for reducing LDL-cholesterol levels in blood comprising the administration of a combination of at least two different anti- PCSK9 antagonist antibodies or an anti-PCSK9 antagonist antibody (e.g., bispecific or bifunctional antibody) directed to different epitopes of PCSK9 protein. The subject single or combination treatment can be used in the prevention and/or treatment of cholesterol and lipoprotein metabolism disorders, including hypercholesterolemia, dyslipidemia, hyperlipidemia, atherosclerosis, acute coronary syndrome and, more generally, cardiovascular disease (CVD).

Anti-gitr antibodies and methods of use thereof

The present invention provides antibodies that bind Glucocorticoid Induced Tumor necrosis factor Receptor family related protein (GITR) and methods of using same. The anti-GITR antibodies can be used therapeutically alone or in combination with other therapeutics to treat cancer and other diseases.

Antagonist antibodies directed against calcitonin gene-related peptide and methods using same

本发明描述了通过施用抗CGRP拮抗剂抗体来预防或治疗CGRP相关病症如血管运动症状的方法，所述病症包括头痛(例如偏头痛、丛集性头痛和紧张性头痛)和热潮红。也描述了针对CGRP的拮抗剂抗体G1和来自G1的抗体。

Engineered polypeptide conjugates and methods for making thereof using transglutaminase

The present invention provides engineered polypeptide conjugates (e.g., antibody-drug-conjugates, toxin-(biocompatible polymer) conjugates, antibody-(biocompatible polymer) conjugates, and bispecific antibodies) comprising acyl donor glutamine-containing tags and amine donor agents. In one aspect, the invention provides an engineered Fc-containing polypeptide conjugate comprising the formula (Fc-containing polypeptide)-T-A, wherein T is an acyl donor glutamine-containing tag engineered at a specific site or comprises an endogenous glutamine made reactive by the Fc-containing polypeptide engineering, wherein A is an amine donor agent, and wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag or the endogenous glutamine. The invention also provides methods of making engineered polypeptide conjugates using transglutaminase.

ANTI NOTCH-1 ANTIBODIES

SE REFIERE A UN ANTICUERPO O UNA PORCION DE UNION AL ANTIGENO DEL MISMO QUE SE UNE A NOTCH-1 QUE COMPRENDE: i) UNA REGION VARIABLE CDR1 DE LA CADENA PESADA QUE COMPRENDE LA SECUENCIA DE AMINOACIDOS DE SEQ ID Nº 18; ii) UNA REGION VARIABLE CDR2 DE LA CADENA PESADA QUE COMPRENDE LA SECUENCIA DE AMINOACIDOS DE SEQ ID Nº 19; iii) UNA REGION VARIABLE CDR3 DE LA CADENA PESADA QUE COMPRENDE LA SECUENCIA DE AMINOACIDOS DE SEQ ID Nº 20; iv) UNA REGION VARIABLE CDR1 DE LA CADENA LIVIANA QUE COMPRENDE LA SECUENCIA DE AMINOACIDOS DE SEQ ID Nº 12; v) UNA REGION VARIABLE CDR2 DE LA CADENA LIVIANA QUE COMPRENDE LA SECUENCIA DE AMINOACIDOS DE SEQ ID Nº 13; Y vi) UNA REGION VARIABLE CDR3 DE LA CADENA LIVIANA QUE COMPRENDE LA SECUENCIA DE AMINOACIDOS DE SEQ ID Nº 14. TAMBIEN SE REFIERE A UNA COMPOSICION FARMACEUTICA QUE CONTIENE DICHO ANTICUERPO SIENDO UTIL EN EL TRATAMIENTO DE CANCER REFERS TO AN ANTIBODY OR AN ANTIGEN-BINDING PORTION OF THE SAME THAT IS JOINED TO NOTCH-1, INCLUDING: i) A HEAVY-DUTY CHAIN VARIABLE CDR1 REGION INCLUDING THE SEQ ID NO. 18 AMINO ACID SEQUENCE; ii) A VARIABLE REGION CDR2 OF THE HEAVY CHAIN INCLUDING THE SEQUENCE OF AMINO ACIDS OF SEQ ID No. 19; iii) A VARIABLE CDR3 REGION OF THE HEAVY CHAIN THAT INCLUDES THE SEQUENCE OF AMINO ACIDS OF SEQ ID NO 20; iv) A VARIABLE REGION CDR1 OF THE LIGHT CHAIN INCLUDING THE SEQUENCE OF AMINO ACIDS OF SEQ ID No. 12; v) A VARIABLE REGION CDR2 OF THE LIGHT CHAIN INCLUDING THE SEQUENCE OF AMINO ACIDS OF SEQ ID No. 13; AND vi) A CDR3 VARIABLE REGION OF THE LIGHT CHAIN THAT INCLUDES THE SEQ ID NUMBER 14 AMINO ACID SEQUENCE. ALSO REFERS TO A PHARMACEUTICAL COMPOSITION THAT CONTAINS SUCH ANTIBODY BEING USEFUL IN THE TREATMENT OF CANCER

Anti notch-1 antibodies

This invention is directed toward monoclonal antibodies that bind specifically to Notch1. In one embodiment, the antibodies binds to at least a first epitope and a second epitope, wherein the first epitope resides with the LinA domain of the NotchI negative regulatory region (NRR), and the second epitope resides within the HD-C domain of the Notch1 NRR.

Methods for treating taxol-induced sensory neuropathy

This invention relates to the field of taxol-induced neuropathy. More specifically, the invention relates to methods of treating taxol-induced sensory neuropathy comprising administration of agonist anti-trkC antibody for the treatment, prevention, and/or amelioration of a symptom of taxol-induced sensory neuropathy.

Methods for treating taxol-induced gut disorder

METHODS OF TREATMENT OF DISEASES OF THE LOWER MOTOR NEURONE AND COMPOSITIONS USED IN THE SAME

Métodos para el tratamiento, prevencion y/o disminucion de los síntomas relacionados con enfermedades de la neurona motora inferior (tales como la atrofia muscular espinal). Los métodos comprenden la administracion de un agonista de un anticuerpo anti-trkC. También se proveen composiciones y conjuntos de elementos (kits). Reivindicacion 1: Una composicion farmacéutica caracterizada porque comprende un anticuerpo agonista anti-trkC y un vehículo aceptable para el uso farmacéutico para tratar una enfermedad de las neuronas motoras inferiores en un individuo. Methods for the treatment, prevention and / or reduction of symptoms related to diseases of the lower motor neuron (such as spinal muscular atrophy). The methods comprise the administration of an agonist of an anti-trkC antibody. Compositions and sets of elements (kits) are also provided. Claim 1: A pharmaceutical composition characterized in that it comprises an anti-trkC agonist antibody and a vehicle acceptable for pharmaceutical use to treat a lower motor neuron disease in an individual.

high drug loading antibody-drug conjugates

a presente invenção fornece conjugados de anticorpo-fármaco mediados por transglutaminase com alta proporção de anticorpo-fármaco (dar) compreendendo 1) marcadores que contêm glutamina, glutaminas endógenas e/ou glutaminas endógenas tornadas reativas pela manipulação do anticorpo ou uma transglutaminase manipulada (por exemplo, com especificidade de substrato alterado); e 2) agentes doa-dores de amina que compreendem unidades doadoras de amina, ligantes e porções do agente, em que dar é de pelo menos cerca de 5. a invenção também se refere aos métodos de produção e métodos de uso de tais conjugados de anticorpo-fármaco altamente carregados de fármaco. The present invention provides high antibody-drug ratio (dar) transglutaminase mediated antibody-drug conjugates comprising 1) markers containing glutamine, endogenous glutamines and / or endogenous glutamines made reactive by antibody manipulation or a manipulated transglutaminase (e.g. , with altered substrate specificity); and 2) amine donor agents comprising amine donor units, binders and portions of the agent, wherein the donor is at least about 5. The invention also relates to methods of production and methods of using such conjugates of highly drug-loaded antibody-drug.

Methods for treating osteoarthritis pain by administering a nerve growth factor antagonist and compositions containing the same

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Methods for treating pain by administering an antagonist antibody against the nerve growth factor and an opioid analgesic, and compositions containing the same

The present invention features methods for treating or preventing pain comprising administering an amount of an antagonist antibody against the nerve growth factor and an amount of an opioid analgesic such that together they provide effective pain relief. The invention also features compositions comprising an antagonist antibody against the nerve growth factor antagonist and an opioid analgesic and kits containing the same.

Method for treating pain by administering a nerve growth factor antagonist and an NSAID and composition containing the same

The present invention features methods for treating or preventing pain comprising administering an amount of a nerve growth factor antagonist (such as an anti-NGF antibody) and an amount of an NSAID such that together they provide effective pain relief. The invention also features compositions comprising a nerve growth factor antagonist and an NSAID and kits containing the same.

Methods for treating bone cancer pain by administering a nerve growth factor antagonistic antibody

The invention features methods and compositions for preventing or treating bone cancer pain including cancer pain associated with bone metastasis by administering an antagonist of nerve growth factor (NGF) which is a humanised anti-NGF antibody that is capable of binding hNGF.

Anti-NGF antibodies and methods using same

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Antibodies directed against amyloid-beta peptide and methods using same

Monoclonal antibody 9TL and antibodies derived from 9TL directed against amyloid-beta peptide and methods of using same for diagnosing and treatment of Alzheimer's disease and Aβ; peptide associated diseases are described. Methods of using antibodies directed against amyloid-beta peptide having impaired effector function for treatment of Alzheimer's disease and Aβ; peptide associated diseases are also described.

Antagonist antibodies directed against calcitonin gene-related peptide and methods using same

The invention features methods for preventing or treating CGRP associated disorders such as vasomotor symptoms, including headaches (e.g., migraine, cluster headache, and tension headache) and hot flushes, by administering an anti-CGRP antagonist antibody. Antagonist antibody G1 and antibodies derived from G1 directed to CGRP are also described.

Antibodies specific for trop-2 and their uses

The present invention provides antibodies that specifically bind to trophoblast cell-surface antigen-2 (Trop-2). The invention further provides antibody conjugates comprising such antibodies, antibody encoding nucleic acids, and methods of obtaining such antibodies. The invention further relates to therapeutic methods for use of these antibodies and Trop-2 antibody conjugates for the treatment of a condition associated with Trop-2 expression (e.g., cancer), such as colon, esophageal, gastric, head and neck, lung, ovarian, or pancreatic cancer.

Human growth hormone receptor antagonist antibodies and methods of use thereof

The present invention provides antagonizing antibodies that bind to growth hormone receptor (GHR). The invention further relates to therapeutic methods for use of these antibodies to reduce IGF-1 levels and/or for the treatment and/or prevention of diseases associated with excessive IGF-1, including treatment of acromegaly, gigantism, cancer, diabetic nephropathy, arthritis, and lung inflammation.

Anti-glucagon receptor antibodies and methods of use thereof

The present invention provides antagonizing antibodies that bind to glucagon receptor and methods of using same. The anti-glucagon receptor antibodies can be used therapeutically to lower glucose levels in blood, and can be in the prevention and/or treatment of glucose-related disorders, including diabetes, hyperglycemia, hyperinsulinemia, impaired fasting glucose, impaired glucose tolerance, dyslipidemia, or metabolic syndrome.

Anti-pd-1 antibodies and methods of use thereof

The present discosure provides antagonizing antibodies that bind to programmed cell death protein 1 (PD-1) and methods of using same. The anti-PD-1 antibodies can be used therapeutically alone or in combination with other therapeutics to treat cancer and other diseases.

Anti-gitr antibodies and methods of use thereof

The present invention provides antibodies that bind Glucocorticoid Induced Tumor necrosis factor Receptor family related protein (GITR) and methods of using same. The anti-GITR antibodies can be used therapeutically alone or in combination with other therapeutics to treat cancer and other diseases.

Anti-NGF antibodies and methods using same

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Anti-ngf antibodies and methods using the same in treating pain associated with musculo-skeletal disorders

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Anti-NGF antibodies and methods using same

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Agonist anti-trkC antibodies and methods using same

The invention concerns agonist anti-trkC antibodies, polypeptides, and polynucleotides encoding the same. The invention further concerns use of such antibodies, polypeptides and/or polynucleotides in the treatment and/or prevention of neuropathies, such as sensory neuropathies, including taxol-induced sensory neuropathy, cisplatin-induced sensory neuropathy, and pyridoxine-induced sensory neuropathy.

Methods for treating bone cancer pain by administering a nerve growth factor antagonist

The invention features methods and compositions for preventing or treating bone cancer pain including cancer pain associated with bone metastasis by administering an antagonist of nerve growth factor (NGF). The NGF antagonist may be an anti-NGF (such as an anti-hNGF) antibody that is capable of binding hNGF.

Methods for treating osteoarthitis pain by administering a nerve growth factor antagonist and compositions containing the same

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Methods for treating osteoarthitis pain by administering a nerve growth factor antagonist and compositions containing the same

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Methods of treating ophthalmic diseases

Methods of using inhibitors (including monoclonal antibodies) directed against amyloid-beta peptide for the treatment of ophthalmic diseases such as age-related macular degeneration are described.

Methods of treating ophthalmic diseases

Methods of using inhibitors (including monoclonal antibodies) directed against amyloid-beta peptide for the treatment of ophthalmic diseases such as age-related macular degeneration are described.

Heterodimeric proteins and methods for producing and purifying them

The present invention relates to engineered heteromultimeric proteins, and more specifically, to methods for producing and purifying heterodimeric proteins, such as bispecific antibodies and other heterodimeric proteins comprising immunoglobulin-like hinge sequences. Methods for producing and purifying such engineered heterodimeric proteins and their use in diagnostics and therapeutics are also provided.

Antibodies directed against amyloid-beta peptide and methods using same

ANTAGONIST ANTIBODIES DIRECTED AGAINST CALCITONIN GENE-RELATED PEPTIDE AND METHODS USING THE SAME

Anticorps antagonistes dirigés contre le peptide apparenté au gène de calcitonine, et méthodes l'utilisant La présente invention a pour objet des méthodes pour la prévention et le traitement de troubles associés au CGRP tels que des symptômes vasomoteurs, y compris des céphalées (par exemple la migraine, les céphalées vasculaires de Horton et les céphalées dues à la tension) et les bouffées de chaleur, en administrant un anticorps antagoniste anti-CGRP. L'anticorps antagoniste G1 et des anticorps dérivés de G1 dirigés contre le CGRP sont également décrits.

Methods for treating bone cancer pain by administering a nerve growth factor antagonistic antibody

Engineered polypeptide conjugates and methods for making thereof using transglutaminase

The present invention provides engineered polypeptide conjugates (e.g., antibody- drug-conjugates, toxin-(biocompatible polymer) conjugates, antibody-(biocompatible polymer) conjugates, and bispecific antibodies) comprising acyl donor glutamine-containing tags and amine donor agents. In one aspect, the invention provides an engineered Fc-containing polypeptide conjugate comprising the formula (Fc-containing polypeptide)-T-A, wherein T is an acyl donor glutamine-containing tag engineered at a specific site or comprises an endogenous glutamine made reactive by the Fc-containing polypeptide engineering, wherein A is an amine donor agent, and wherein the amine donor agent is site-specifically conjugated to the acyl donor glutamine-containing tag or the endogenous glutamine. The invention also provides methods of making engineered polypeptide conjugates using transglutaminase.

Methods for treating lower motor neuron diseases and compositions for the same

This invention provides methods for the treatment, prevention, and/or amelioration of symptoms relating to lower motor neuron diseases (such as spinal muscular atrophy). The methods comprise administration of an agonist anti-trkC antibody. Compositions and kits are also provided.

Methods for treating cardiac arrhythmia and preventing death due to cardiac arrhythmia using ngf antagonists

This invention relates to the field of cardiac disease. More specifically, the invention relates to methods using an NGF antagonist for treating and preventing cardiac arrhythmia and methods of preventing death due to cardiac arrhythmia.

T cell receptor knock out engineered immune cells, endowed with chimeric antigen receptors binding to cd123 for the treatment of relapsed/refractory acute myeloid lymphoma or blastic plasmacytoid dendritic cell neoplasm

The present invention relates to a TCRKO - or TCR KOand dCK KO - engineered immune cells expressing a Chimeric Antigen Receptors (CAR) specific for CD123 that is a recombinant chimeric protein able to redirect immune cell specificity and reactivity toward CD123-expressing cells, and more particularly in which extracellular ligand binding is a scFV derived from a CD123 monoclonal antibody, conferring specific immunity against CD123 positive cells. The engineered immune cells endowed with such CD123 CARs are particularly suited for treating relapse refractory AML and blastic plasmacytoid dendritic cell neoplasmand for use as a treatment before bone marrow transplantation.

Anti-ngf antibodies and methods using the same

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

METHODS OF TREATMENT OF PAIN CAUSED BY OSTEOARTRITIS THROUGH THE ADMINISTRATION OF AN ANTAGONIST OF THE NEURONAL GROWTH FACTOR AND COMPOSITIONS CONTAINING IT

Anticuerpos anti-NGF (tales como anticuerpos de antagonistas anti-NGF), y polinucleotidos que los codifican. Uso de dichos anticuerpos y/o polinucleotidos en el tratamiento y/o prevencion del dolor, incluyendo el dolor, incluyendo el dolor post- quirurgico, el dolor de la artritis reumatoide y el dolor causado por la osteoartritis. Anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides that encode them. Use of said antibodies and / or polynucleotides in the treatment and / or prevention of pain, including pain, including post-surgical pain, rheumatoid arthritis pain and pain caused by osteoarthritis.

Antibody-drug conjugates with high drug loading

Antibodies with binding of ph dependent antigens.

La presente invención se refiere a anticuerpos con unión dependiente de pH a su antígeno de tal forma que la afinidad de unión al antígeno a pH fisiológico (es decir, pH 7,4) es mayor que a pH endosómico (es decir, pH 6,0 o 5,5). En otras palabras, la proporción de Ko la proporción de ka pH 5,5/pH 7,4 o a pH 6,0/pH 7,4 es más de, ovaría entre, 2, 3, 4, 8, 10, 16, 20, 30, 40, o 100 o más. Tales anticuerpos dependientes de pH se disocian preferencialmente del antígeno en el endosoma. Esto puede incrementar la semivida del anticuerpo, en comparación con los anticuerpos con KD equivalentes a pH 7,4 pero con ninguna unión dependiente de pH, cuando el antígeno es uno que sufre la eliminación mediada por antígeno (por ejemplo, PCSK9). Los anticuerpos con unión dependiente de pH pueden disminuir la semivida de antígeno total cuando el antígeno sufre eliminación reducida cuando se une a anticuerpo (por ejemplo, 1L6). Los anticuerpos con unión dependiente de pH también pueden prolongar el decrecimiento en antígeno que no está unido a anticuerpo. Esto puede ser importante cuando se antagoniza un antígeno objetivo típicamente presente a niveles altos (por ejemplo, IgE, DKK1, C5 y SOST). Además, tales anticuerpos pueden incrementar la semivida de antígeno cuando el antígeno es un receptor y el receptor tiene eliminación incrementada cuando se une a anticuerpo (por ejemplo, receptor de GMCSF). The present invention relates to antibodies with pH-dependent binding to their antigen such that the affinity of binding to the antigen at physiological pH (i.e., pH 7.4) is greater than at endosomal pH (i.e., pH 6, 0 or 5.5). In other words, the proportion of Ko the proportion of ka pH 5.5 / pH 7.4 or pH 6.0 / pH 7.4 is more than, would vary between, 2, 3, 4, 8, 10, 16, 20, 30, 40, or 100 or more. Such pH-dependent antibodies preferentially dissociate from the antigen in the endosome. This may increase the half-life of the antibody, compared to antibodies with KD equivalent to pH 7.4 but ...

Methods for treating lower motor neuron diseases and compositions for the same

This invention provides methods for the treatment, prevention, and/or amelioration of symptoms relating to lower motor neuron diseases (such as spinal muscular atrophy). The methods comprise administration of an agonist anti-trkC antibody. Compositions and kits are also provided.

Methods for treating post-surgical pain by administering an anti-nerve growth factor antagonist antibody and compositions containing the same

Anti-pd-1 antibodies

La presente invención se refiere a anticuerpos antagonistas que se fijan a la proteína de muerte celular programada 1 (PD-1) que comprenden una región variable de la cadena pesada (VH) que comprende una región determinante de la complementariedad uno (CDR1) de VH, CDR2 VH y CDR3 VH de la VH que tienen una secuencia de aminoácidos seleccionada del grupo que consiste en SEQ ID NO: 3, SEQ ID NO: 4; SEQ ID NO: 5; y SEQ ID NO: 6; y una región variable de la cadena liviana (VL) que comprende una CDR1 VL, CDR2 VL y CDR3 VL de la VL que tienen una secuencia de aminoácidos seleccionada del grupo que consiste en SEQ ID NO: 2; SEQ ID NO:7; SEQ ID NO: 8; y SEQ ID NO: 9; para el tratamiento, la prevención y/o el diagnóstico de distintas enfermedades, que incluyen enfermedades hiperproliferativas, tales como cáncer. The present invention relates to antagonistic antibodies that bind to programmed cell death protein 1 (PD-1) comprising a variable region of the heavy chain (VH) comprising a complementarity determining region one (CDR1) of VH , VH CDR2 and VH CDR3 having an amino acid sequence selected from the group consisting of SEQ ID NO: 3, SEQ ID NO: 4; SEQ ID NO: 5; and SEQ ID NO: 6; and a light chain variable region (VL) comprising a VL CDR1, VL CDR2, and VL CDR3 VL having an amino acid sequence selected from the group consisting of SEQ ID NO: 2; SEQ ID NO: 7; SEQ ID NO: 8; and SEQ ID NO: 9; for the treatment, prevention and / or diagnosis of various diseases, including hyperproliferative diseases, such as cancer.

Antibodies directed to amyloid beta peptide and methods for its use

T cell receptor knock out engineered immune cells, endowed with chimeric antigen receptors binding to CD123 for the treatment of relapsed/refractory acute myeloid lymphoma or blastic plasmacytoid dendritic cell neoplasm

The present invention relates to a TCRKO - or TCR KOand dCK KO - engineered immune cells expressing a Chimeric Antigen Receptors (CAR) specific for CD123 that is a recombinant chimeric protein able to redirect immune cell specificity and reactivity toward CD123-expressing cells, and more particularly in which extracellular ligand binding is a scFV derived from a CD123 monoclonal antibody, conferring specific immunity against CD123 positive cells. The engineered immune cells endowed with such CD123 CARs are particularly suited for treating relapse refractory AML and blastic plasmacytoid dendritic cell neoplasmand for use as a treatment before bone marrow transplantation.

Anti-ngf antibodies and methods using same

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

PCSK9 antagonists

Abstract The present invention provides antagonizing antibodies, antigen-binding portions thereof, and aptamers that bind to proprotein convertase subtilisin kexin type 9 (PCSK9). Also provided are antibodies directed to peptides, in which the antibodies bind to PCSK9. The invention further provides a method of obtaining such antibodies and antibody-encoding nucleic acid. The invention further relates to therapeutic methods for use of these antibodies and antigen binding portions thereof to reduce LDL-cholesterol levels and/or for the treatment and/or prevention of cardiovascular disease, including treatment of hypercholes-terolemia.

Anti-ngf antibodies and methods using same

The invention concerns anti-NGF antibodies (such as anti-NGF antagonist antibodies), and polynucleotides encoding the same. The invention further concerns use of such antibodies and/or polynucleotides in the treatment and/or prevention of pain, including post-surgical pain, rheumatoid arthritis pain, and osteoarthritis pain.

Method of treating Alzheimer's disease using antibodies directed against amyloid beta peptide and compositions thereof